The overall objective of this research is to compare and contrast the biological activity and the biochemical nature of tumor-specific helper factors in three syngeneic guinea pig tumor models. Tumor-specific helper factors have been consistently demonstrated in the line-10 hepatocarcinoma system and the biological activity and kinetics of tumor-specific helper activity has been determined. The L2C leukemia and line-1 hepatocarcinoma system have been more difficult to characterize. In the case of the L2C leukemia, tumor-specific helper factors have been isolated, but the reproducibility of results has been less than that achieved with the line-10 hepatocarcinoma. Experiments to date with the line-1 hepatocarcinoma have not demonstrated tumor-specific helper factors. It is a major objective of this research to optimize recovery of tumor-specific helper factors in the L2C system and to fully determine whether helper factors can be isolated in the line-1 hepatocarcinoma system. To achieve this goal, modifications in tumor dosage and tumor development will be employed in conjunction with a rigorous evaluation of multiple time frames for in vitro demonstration of tumor-specific helper factors. Preliminary results suggest that the L2C leukemia will yield results with the modified protocol, while no statement can be made regarding the line-1 hepatocarcinoma. Both the in vitro and the in vivo biological activity of isolated tumor-specific helper factors will be determined in conjunction with biochemical analysis and determination of antigenic make-up of each factor. In the case of line-10 tumor-specific helper factors, this analysis is in progress or completed and, in selected cases, such analysis is progressing with the L2C leukemia. The similarities and dissimilarities for each set of factors will be determined by: 51Cr release assay, isoelectric focusing, polyacrylamide gel electrophoresis and by selective depletion of biological activity by use of specific antisera. Relatively large quantities of each set of factors will be stored and evaluated for in vivo activity and specificity in tumor-suppressive experiments. In the case of the line-10 system, this may be facilitated through the use and characterization of an established line-10-specific helper cell population.